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1.
J Agric Food Chem ; 69(36): 10515-10526, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34463509

RESUMO

As a natural flavonolignan, silibinin is reported to possess multiple biological activities, while the inhibitory potential of silibinin on carbohydrate-hydrolyzing enzymes is still unclear. Therefore, in this study, the inhibitory effect and underlying mechanism of silibinin against α-amylase/α-glucosidase were investigated. The results indicated that silibinin showed a strong inhibitory efficiency against α-amylase/α-glucosidase in noncompetitive manners and exhibited synergistic inhibition against α-glucosidase with acarbose. However, interestingly, the inhibitory effect of silibinin was significantly hindered in various milk protein-rich environments, but this phenomenon disappeared after simulated gastrointestinal digestion of milk proteins in vitro. Furthermore, silibinin could combine with the inactive site of α-amylase/α-glucosidase and change the microenvironment and secondary structure of the enzymes, thereby influencing the catalytic efficiency of enzymes. This research suggested that silibinin could be used as a novel carbohydrate-hydrolyzing enzyme inhibitor, and milk beverages rich in silibinin had the potential for further application in antidiabetic dietary or medicine.


Assuntos
Acarbose , alfa-Glucosidases , Acarbose/farmacologia , Amilases , Glucosidases , Inibidores de Glicosídeo Hidrolases , Proteínas do Leite , Silibina , alfa-Amilases
2.
Nutrients ; 13(8)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34444986

RESUMO

Postprandial hypotension (PPH) is an important and under-recognised disorder resulting from inadequate compensatory cardiovascular responses to meal-induced splanchnic blood pooling. Current approaches to management are suboptimal. Recent studies have established that the cardiovascular response to a meal is modulated profoundly by gastrointestinal factors, including the type and caloric content of ingested meals, rate of gastric emptying, and small intestinal transit and absorption of nutrients. The small intestine represents the major site of nutrient-gut interactions and associated neurohormonal responses, including secretion of glucagon-like peptide-1, glucose-dependent insulinotropic peptide and somatostatin, which exert pleotropic actions relevant to the postprandial haemodynamic profile. This review summarises knowledge relating to the role of these gut peptides in the cardiovascular response to a meal and their potential application to the management of PPH.


Assuntos
Pressão Sanguínea , Polipeptídeo Inibidor Gástrico/sangue , Fármacos Gastrointestinais/farmacologia , Peptídeo 1 Semelhante ao Glucagon/sangue , Hipotensão , Período Pós-Prandial , Somatostatina/sangue , Acarbose/farmacologia , Acarbose/uso terapêutico , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Fármacos Gastrointestinais/uso terapêutico , Glucagon/sangue , Receptor do Peptídeo Semelhante ao Glucagon 1/sangue , Humanos , Hipotensão/tratamento farmacológico , Hipotensão/fisiopatologia , Insulina/sangue , Peptídeos , Circulação Esplâncnica
3.
Molecules ; 26(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34361791

RESUMO

As a key enzyme regulating postprandial blood glucose, α-Glucosidase is considered to be an effective target for the treatment of diabetes mellitus. In this study, a simple, rapid, and effective method for enzyme inhibitors screening assay was established based on α-glucosidase catalyzes reactions in a personal glucose meter (PGM). α-glucosidase catalyzes the hydrolysis of maltose to produce glucose, which triggers the reduction of ferricyanide (K3[Fe(CN)6]) to ferrocyanide (K4[Fe(CN)6]) and generates the PGM detectable signals. When the α-glucosidase inhibitor (such as acarbose) is added, the yield of glucose and the readout of PGM decreased accordingly. This method can achieve the direct determination of α-glucosidase activity by the PGM as simple as the blood glucose tests. Under the optimal experimental conditions, the developed method was applied to evaluate the inhibitory activity of thirty-four small-molecule compounds and eighteen medicinal plants extracts on α-glucosidase. The results exhibit that lithospermic acid (52.5 ± 3.0%) and protocatechualdehyde (36.8 ± 2.8%) have higher inhibitory activity than that of positive control acarbose (31.5 ± 2.5%) at the same final concentration of 5.0 mM. Besides, the lemon extract has a good inhibitory effect on α-glucosidase with a percentage of inhibition of 43.3 ± 3.5%. Finally, the binding sites and modes of four active small-molecule compounds to α-glucosidase were investigated by molecular docking analysis. These results indicate that the PGM method is feasible to screening inhibitors from natural products with simple and rapid operations.


Assuntos
Benzaldeídos/farmacologia , Benzofuranos/farmacologia , Glicemia/análise , Catecóis/farmacologia , Depsídeos/farmacologia , Diabetes Mellitus Tipo 2/diagnóstico , Inibidores de Glicosídeo Hidrolases/farmacologia , Monitorização Ambulatorial/métodos , alfa-Glucosidases/sangue , Acarbose/química , Acarbose/farmacologia , Benzaldeídos/química , Benzaldeídos/isolamento & purificação , Benzofuranos/química , Benzofuranos/isolamento & purificação , Sítios de Ligação , Técnicas Biossensoriais/instrumentação , Catecóis/química , Catecóis/isolamento & purificação , Depsídeos/química , Depsídeos/isolamento & purificação , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores de Glicosídeo Hidrolases/química , Humanos , Hidrólise , Cinética , Maltose/metabolismo , Simulação de Acoplamento Molecular , Monitorização Ambulatorial/instrumentação , Extratos Vegetais/química , Plantas Medicinais , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Termodinâmica , Dispositivos Eletrônicos Vestíveis , alfa-Glucosidases/química
4.
Expert Opin Investig Drugs ; 30(7): 749-758, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34081543

RESUMO

Introduction:Several pharmacological drugs have shown proof of concept for longevity in animal models. I aimed to identify and review those longevity drug candidates that are undergoing clinical trials.Areas covered:Recent (post-2017) longevity clinical trials were found in US and EU clinical trial registries. Longevity drug candidates are the antidiabetic drugs metformin and acarbose, and the immunosuppressant rapamycin. These medicinal drugs are tested on biochemical and clinical markers of aging. In addition, vitamin D supplementation is being investigated in two mega-trials (sample size> 5000) for its efficacy in reducing all-cause mortality.Expert opinion:Anti-aging effects of longevity drug candidates suggest, but do not demonstrate that they prolong life. The two megatrials with vitamin D supplementation make it possible to detect differences in life expectancy between vitamin D and placebo. Therefore, a protocol similar to that for vitamin D could be used to demonstrate pro-longevity effects of metformin, acarbose, and rapamycin.


Assuntos
Envelhecimento/efeitos dos fármacos , Drogas em Investigação/farmacologia , Longevidade/efeitos dos fármacos , Acarbose/farmacologia , Envelhecimento/fisiologia , Animais , Humanos , Longevidade/fisiologia , Metformina/farmacologia , Nutrientes/farmacologia , Sirolimo/farmacologia
5.
Food Chem ; 361: 130047, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34029903

RESUMO

Inhibition of maltase, sucrase, isomaltase and glucoamylase activity by acarbose, epigallocatechin gallate, epicatechin gallate and four polyphenol-rich tea extract from white, green, oolong, black tea, were investigated by using rat intestinal enzymes and human Caco-2 cells. Regarding rat intestinal enzyme mixture, all four tea extracts were very effective in inhibiting maltase and glucoamylase activity, but only white tea extract inhibited sucrase and isomaltase activity and the inhibition was limited. Mixed-type inhibition on rat maltase activity was observed. Tea extracts in combination with acarbose, produced a synergistic inhibitory effect on rat maltase activity. Caco-2 cells experiments were conducted in Transwells. Green tea extract and epigallocatechin gallate show dose-dependent inhibition on human sucrase activity, but no inhibition on rat sucrase activity. The opposite was observed on maltase activity. The results highlighted the different response in the two investigated model systems and show that tea polyphenols are good inhibitors for α-glucosidase activity.


Assuntos
Glicosídeo Hidrolases/antagonistas & inibidores , Intestinos/enzimologia , Extratos Vegetais/química , Polifenóis/farmacologia , Chá/química , Acarbose/farmacologia , Animais , Células CACO-2 , Catequina/análogos & derivados , Catequina/farmacologia , Glucana 1,4-alfa-Glucosidase/antagonistas & inibidores , Inibidores de Glicosídeo Hidrolases/farmacologia , Humanos , Cinética , Oligo-1,6-Glucosidase/antagonistas & inibidores , Ratos , Sacarase/antagonistas & inibidores , alfa-Glucosidases/efeitos dos fármacos
6.
ACS Appl Mater Interfaces ; 13(22): 25624-25634, 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34043318

RESUMO

A highly stable and reusable fluorescent multisample nanobiosensor for the detection of α-glucosidase inhibitors has been developed by coupling fluorescent liposomal nanoparticles based on conjugated polymers (L-CPNs) to the enzyme α-glucosidase, one of the main target enzymes in the treatment of type 2 diabetes. The mechanism of sensing is based on the fluorescence "turn-on" of L-CPNs by p-nitrophenol (PNP), the end product of the enzymatic hydrolysis of p-nitrophenyl-α-d-glucopyranoside. L-CPNs, composed of lipid vesicles coated with a blue-emitting cationic polyfluorene, were designed and characterized to obtain a good response to PNP. Two nanobiosensor configurations were developed in this study. In the first step, a single-sample nanobiosensor composed of L-CPNs and α-glucosidase entrapped in a sol-gel glass was developed in order to characterize and optimize the device. In the second part, the nanobiosensor was integrated and adapted to a multiwell microplate and the possibility of reusing it and performing multiple measurements simultaneously with samples containing different α-glucosidase inhibitors was investigated. Using super-resolution confocal microscopy, L-CPNs could be visualized within the sol-gel matrix, and the quenching of their fluorescence, induced by the substrate, was directly observed in situ. The device was also shown to be useful not only as a platform for screening of antidiabetic drugs but also for quantifying their presence. The latter application was successfully tested with the currently available drug, acarbose.


Assuntos
Técnicas Biossensoriais/métodos , Fluorescência , Inibidores de Glicosídeo Hidrolases/farmacologia , Hipoglicemiantes/farmacologia , Nanopartículas/administração & dosagem , Polímeros/química , alfa-Glucosidases/química , Acarbose/farmacologia , Fluorenos/química , Corantes Fluorescentes , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Humanos , Hipoglicemiantes/isolamento & purificação , Lipossomos/química , Nanopartículas/química , alfa-Glucosidases/análise
7.
Med Microbiol Immunol ; 210(2-3): 133-147, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33870453

RESUMO

Treatment against visceral leishmaniasis (VL) is mainly hampered by drug toxicity, long treatment regimens and/or high costs. Thus, the identification of novel and low-cost antileishmanial agents is urgent. Acarbose (ACA) is a specific inhibitor of glucosidase-like proteins, which has been used for treating diabetes. In the present study, we show that this molecule also presents in vitro and in vivo specific antileishmanial activity against Leishmania infantum. Results showed an in vitro direct action against L. infantum promastigotes and amastigotes, and low toxicity to mammalian cells. In addition, in vivo experiments performed using free ACA or incorporated in a Pluronic® F127-based polymeric micelle system called ACA/Mic proved effective for the treatment of L. infantum-infected BALB/c mice. Treated animals presented significant reductions in the parasite load in their spleens, livers, bone marrows and draining lymph nodes when compared to the controls, as well as the development of antileishmanial Th1-type humoral and cellular responses based on high levels of IFN-γ, IL-12, TNF-α, GM-CSF, nitrite and IgG2a isotype antibodies. In addition, ACA or ACA-treated animals suffered from low organ toxicity. Treatment with ACA/Mic outperformed treatments using either Miltefosine or free ACA based on parasitological and immunological evaluations performed one and 15 days post-therapy. In conclusion, data suggest that the ACA/Mic is a potential therapeutic agent against L. infantum and merits further consideration for VL treatment.


Assuntos
Acarbose/farmacologia , Acarbose/uso terapêutico , Imunidade , Leishmania infantum/efeitos dos fármacos , Leishmania infantum/imunologia , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/imunologia , Animais , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Reposicionamento de Medicamentos , Feminino , Leishmaniose Visceral/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Micelas , Carga Parasitária , Fosforilcolina/análogos & derivados , Fosforilcolina/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Resultado do Tratamento
8.
Eur J Endocrinol ; 184(3): 383-394, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33449919

RESUMO

Aims: The alpha-glucosidase inhibitor acarbose is believed to reduce plasma glucose by delaying hydrolysis of carbohydrates. Acarbose-induced transfer of carbohydrates to the distal parts of the intestine increases circulating glucagon-like peptide 1 (GLP-1). Using the GLP-1 receptor antagonist exendin(9-39)NH2, we investigated the effect of acarbose-induced GLP-1 secretion on postprandial glucose metabolism in patients with type 2 diabetes. Methods: In a double-blinded, placebo-controlled, randomized, crossover study, 15 participants with metformin-treated type 2 diabetes (age: 57-85 years, HbA1c: 40-74 mmol/mol) were subjected to two 14-day treatment periods with acarbose or placebo, respectively, separated by a 6-week wash-out period. At the end of each period, two randomized 4-h liquid mixed meal tests with concomitant infusion of exendin(9-39)NH2 and saline, respectively, were performed. Results: Compared to placebo, acarbose increased postprandial GLP-1 concentrations and decreased postprandial glucose. We observed no absolute difference in the exendin(9-39)NH2-induced increase in postprandial glucose excursions between placebo and acarbose periods, but relatively, postprandial glucose was increased by 119 ± 116% (mean ± s.d.) during exendin(9-39)NH2 infusion in the acarbose period vs a 39 ± 27% increase during the placebo period (P = 0.0163). Conclusions: We confirm that acarbose treatment stimulates postprandial GLP-1 secretion in patients with type 2 diabetes. Using exendin(9-39)NH2, we did not see an impact of acarbose-induced GLP-1 secretion on absolute measures of postprandial glucose tolerance, but relatively, the effect of exendin(9-39)NH2 was most pronounced during acarbose treatment.


Assuntos
Acarbose/farmacologia , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/metabolismo , Peptídeo 1 Semelhante ao Glucagon/fisiologia , Período Pós-Prandial/efeitos dos fármacos , Acarbose/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Glicemia/metabolismo , Estudos Cross-Over , Dinamarca , Diabetes Mellitus Tipo 2/tratamento farmacológico , Método Duplo-Cego , Feminino , Esvaziamento Gástrico/efeitos dos fármacos , Humanos , Resistência à Insulina , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Placebos
9.
Diabetes Res Clin Pract ; 172: 108489, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33035600

RESUMO

AIM: To assess the relationship between acarbose and hepatotoxicity, cardiovascular disease (CVD), and mortality among type 2 diabetes (T2D) patients with end-stage renal disease (ESRD). METHODS: 32,531 T2D patients with ESRD were identified from Taiwan's National Health Insurance Research Database in 2000~∼2012 and followed up until 2013. 19.3% of subjects were newly initiated with acarbose during the follow-up. The use of acarbose was quantified as the numbers of the 30-day drug's supplies and dosages (measured by defined daily doses; DDDs), respectively. Time-varying Cox models were applied to evaluate the association of acarbose use with hepatic, cardiovascular and mortality outcomes, with adjustment for patients' demographics, comorbidities, diabetes severity, and co-medications. RESULTS: For each 30-day supply increase in acarbose exposure, the risks of hepatic injury, composite CVD events, and all-cause mortality were significantly lowered by 9% (95% confidence interval: 6-12%), 7% (6-7%) and 7% (7-8%), respectively, while for each 30-day DDD increase in acarbose exposure, the risks for three aforementioned outcomes were significantly reduced by 45% (33-54%), 33% (29-36%) and 35% (32-39%), respectively. In subgroup analyses, the favorable study outcomes of acarbose use were more apparent among patients with more severe diabetes, a longer diabetes duration, or absence of established CVD at baseline. CONCLUSION: Acarbose used in real-world T2D patients with ESRD may have hepatic and cardiovascular safety.


Assuntos
Acarbose/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores de Glicosídeo Hidrolases/uso terapêutico , Falência Renal Crônica/induzido quimicamente , Acarbose/farmacologia , Feminino , Inibidores de Glicosídeo Hidrolases/farmacologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade
10.
Nat Prod Res ; 35(10): 1596-1604, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-31204495

RESUMO

To find a potent α-glucosidase inhibitor, 24 tyrosol derivatives with different substituents located at the meta, ortho, or para position of the phenyl group have been synthesised via the Mitsunobu reaction, characterised by 1H NMR, 13C NMR, ESI-MS and IR and evaluated for inhibition. The derivatives possessed varying degrees of in vitro inhibitory activity against α-glucosidase and a relationship between the structure and activity was subsequently established for all compounds. Two of these compounds with substituents at the para position showed significant inhibitory effects surpassing that of the control standard acarbose. Molecular docking studies performed to better understand the binding interactions between the enzyme and the two most active compounds showed substantial binding within the active site of α-glucosidase. Taken together, these results indicate that the position of the substituent plays a crucial role in this inhibition and may facilitate the development of new α-glucosidase inhibitors.


Assuntos
Inibidores de Glicosídeo Hidrolases/farmacologia , Simulação de Acoplamento Molecular , Álcool Feniletílico/análogos & derivados , alfa-Glucosidases/metabolismo , Acarbose/química , Acarbose/farmacologia , Sítios de Ligação , Domínio Catalítico , Inibidores de Glicosídeo Hidrolases/química , Álcool Feniletílico/síntese química , Álcool Feniletílico/química , Álcool Feniletílico/farmacologia , Relação Estrutura-Atividade , Leveduras/enzimologia , alfa-Glucosidases/química
11.
Nat Prod Res ; 35(5): 788-791, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30990061

RESUMO

The present study was designed to conduct the bioassay-guided isolation of possible bioactive compound(s) responsible for the antidiabetic action of Xylopia aethiopica (Dunal) A. Rich. fruit. The isolation of compound was guided by α-glycosidase and α-amylase inhibitory activities. Molecular docking with Autodock Vina was used to decipher the mode of interaction and binding affinity of the possible compound(s) with the selected enzymes. A pentacyclic triterpene, oleanolic acid (OA) was isolated from fruit and exhibited significantly (p < 0.05) lower IC50 values (α-amylase: 89.02 ± 1.12 µM, α-glucosidase: 46.05 ± 0.25 µM) than other fractions and the acarbose. Interestingly, OA was found to bind to the α-amylase and α-glucosidase with minimum binding energy values of -0.9 and -1.2 kcal/mol respectively and none of the interactions involved hydrogen bond formation. Data of this study suggest that OA is responsible for the antidiabetic action of X. aethiopica fruit through the inhibition of α-amylase and α-glucosidase enzyme activities.


Assuntos
Bioensaio , Frutas/química , Hipoglicemiantes/farmacologia , Simulação de Acoplamento Molecular , Ácido Oleanólico/isolamento & purificação , Ácido Oleanólico/farmacologia , Xylopia/química , Acarbose/farmacologia , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Inibidores Enzimáticos/farmacologia , Concentração Inibidora 50 , Extratos Vegetais/farmacologia , Espectroscopia de Prótons por Ressonância Magnética , alfa-Amilases/antagonistas & inibidores , alfa-Glucosidases/metabolismo
12.
Mol Med Rep ; 23(1)2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33236139

RESUMO

Pancreatic and duodenal homeobox (PDX)­1 is a gene that plays an important role in pancreatic development and function. Type­2 diabetes mellitus (T2DM) is a metabolic disease associated with insulin resistance and impaired islet ß­cell function. There is evidence that methylation of PDX­1 plays a role in the development of T2DM. Acarbose is an α­glucosidase inhibitor that can effectively delay the absorption of glucose by the body. The aim of the present study was to examine the effect of acarbose on PDX­1 methylation in islet ß­cells in spontaneous type­2 diabetic db/db mice. The effect of acarbose on glucose and lipid metabolism in these mice was assessed by measuring food intake, body weight, glycated hemoglobin (HbA1c), glucagon, serum total cholesterol and triglyceride levels, and fasting blood glucose (FBG). Blood glucose levels were also analyzed using intraperitoneal glucose tolerance and insulin tolerance tests. Immunohistochemistry was used to evaluate the effect of acarbose on pathological changes in the pancreas. Moreover, a BrdU assay was used to analyze cell proliferation. Lastly, the effect of acarbose on PDX­1 methylation was evaluated in mice using methylation­specific PCR and western blot analysis. In the present study, body weight significantly increased in the acarbose group, compared to the normal group. The levels of HbA1c and glucagon in the T2DM group significantly increased, compared with the normal group, but significantly decreased in acarbose­treated mice. Moreover, FBG levels significantly decreased in the acarbose groups compared with T2DM mice. Acarbose also promoted cell proliferation, compared with untreated T2DM mice. In addition, PDX­1 methylation and cytoplasmic expression levels were both downregulated in the acarbose group, compared with the T2DM group. In conclusion, these results suggested that acarbose could promote the proliferation of islet ß­cells and inhibit PDX­1 methylation in islet ß cells from diabetic mice. Thus, acarbose may provide a new strategy to treat T2DM.


Assuntos
Acarbose/farmacologia , Metilação de DNA/efeitos dos fármacos , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Proteínas de Homeodomínio/metabolismo , Células Secretoras de Insulina/metabolismo , Transativadores/metabolismo , Animais , Masculino , Camundongos , Camundongos Endogâmicos NOD
13.
Food Chem ; 337: 127788, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32795862

RESUMO

The phenolic compounds composition, antioxidant and antidiabetic properties of eight brown sorghum genotypes were investigated. DPPH radical scavenging activity was highest in SOR 03, followed by SOR 11, SOR 08 and SOR 33. SOR 33, SOR 03, SOR 08, SOR 11 showed the highest ABTS radical scavenging activity. Furthermore, SOR 11, SOR 17 and SOR 33 exhibited significantly higher percentage inhibitory activity of α-glucosidase and α-amylase (IC50 = 14.71, 32.98, 24.93 µg/ml and 27.6, 23.84, 45.01 µg/ml, respectively) compared to acarbose (IC50 = 59.34 and 27.73 µg/ml, respectively). Similarly, SOR 17, SOR 11 and SOR 33 showed significantly potent inhibition of AGEs formation with IC50 values of 14.19, 18.23 and 26.31 µg/ml, respectively, compared to aminoguanidine (AG) (52.30 µg/ml). Flavones, isoflavones and dihydroflavonols were the predominant flavonoids identified in SOR 11, SOR 17 and SOR 33 genotypes. Therefore, these sorghum grains are potential candidates for the development of functional foods.


Assuntos
Antioxidantes/análise , Flavonoides/análise , Hipoglicemiantes/análise , Sorghum/química , alfa-Amilases/antagonistas & inibidores , alfa-Glucosidases , Acarbose/farmacologia , Cromatografia Líquida de Alta Pressão , Grão Comestível/química , Flavonoides/farmacologia , Inibidores de Glicosídeo Hidrolases , Fenóis/análise , Fenóis/farmacologia , Espectrometria de Massas em Tandem
14.
Int J Biol Macromol ; 170: 447-458, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33352159

RESUMO

The objective of present research was to explore whether Sargassum fusiforme polysaccharide (SFP) could partly replace acarbose against type 2 diabetes in rats. Results indicated that SFP co-administered with low-dose acarbose intervention typically mitigated diabetic symptoms and serum profiles and exhibited better anti-diabetic effects than single acarbose treatment in controlling fasting blood glucose, improving insulin resistance and mitigating kidney injuries. The RT-qPCR analysis indicated that SFP co-administered with low-dose acarbose administration distinctly activated the IRS/PI3K/AKT signaling pathway compared with single acarbose treatment. Moreover, the co-administration also restrained liver fat accumulation via affecting the expression of HMGCR and SREBP-1c genes. In addition, the 16S rRNA gene sequencing analysis indicated that SFP co-administered with low-dose acarbose significantly restored beneficial composition of gut flora in diabetic rats, such as the increase of Muribaculaceae, Lachnospiraceae, Bifidobacterium, Ruminococcaceae_UCG-014, Ruminococcus_1, Romboutsia, Eggerthellaceae, Alistipes and Faecalibaculum, and the decrease of Escherichia-Shigella. These results suggested that SFP, the novel natural adjuvant of acarbose, displayed the desirable benefits in minimizing the dose of drug, while improving the anti-diabetic efficiency.


Assuntos
Acarbose/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Polissacarídeos/farmacologia , Sargassum/metabolismo , Animais , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/microbiologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/microbiologia , Modelos Animais de Doenças , Gorduras/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Fígado/efeitos dos fármacos , RNA Ribossômico 16S/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
15.
J Enzyme Inhib Med Chem ; 35(1): 1879-1890, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33003963

RESUMO

A series of novel N-alkyl-1-deoxynojirimycin derivatives 25 ∼ 44 were synthesised and evaluated for their in vitro α-glucosidase inhibitory activity to develop α-glucosidase inhibitors with high activity. All twenty compounds exhibited α-glucosidase inhibitory activity with IC50 values ranging from 30.0 ± 0.6 µM to 2000 µM as compared to standard acarbose (IC50 = 822.0 ± 1.5 µM). The most active compound 43 was ∼27-fold more active than acarbose. Kinetic study revealed that compounds 43, 40, and 34 were all competitive inhibitors on α-glucosidase with Ki of 10 µM, 52 µM, and 150 µM, respectively. Molecular docking demonstrated that the high active inhibitors interacted with α-glucosidase by four types of interactions, including hydrogen bonds, π-π stacking interactions, hydrophobic interactions, and electrostatic interaction. Among all the interactions, the π-π stacking interaction and hydrogen bond played a significant role in a various range of activities of the compounds.


Assuntos
Glucosamina/análogos & derivados , Inibidores de Glicosídeo Hidrolases/síntese química , alfa-Glucosidases/metabolismo , 1-Desoxinojirimicina/síntese química , 1-Desoxinojirimicina/farmacocinética , Acarbose/farmacologia , Acarbose/normas , Compostos de Benzilideno/química , Glucosamina/síntese química , Glucosamina/farmacocinética , Inibidores de Glicosídeo Hidrolases/farmacocinética , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Cinética , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade
16.
JCI Insight ; 5(21)2020 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-32990683

RESUMO

With an expanding aging population burdened with comorbidities, there is considerable interest in treatments that optimize health in later life. Acarbose (ACA), a drug used clinically to treat type 2 diabetes mellitus (T2DM), can extend mouse life span with greater effect in males than in females. Using a genetically heterogeneous mouse model, we tested the ability of ACA to ameliorate functional, pathological, and biochemical changes that occur during aging, and we determined which of the effects of age and drug were sex dependent. In both sexes, ACA prevented age-dependent loss of body mass, in addition to improving balance/coordination on an accelerating rotarod, rotarod endurance, and grip strength test. Age-related cardiac hypertrophy was seen only in male mice, and this male-specific aging effect was attenuated by ACA. ACA-sensitive cardiac changes were associated with reduced activation of cardiac growth-promoting pathways and increased abundance of peroxisomal proteins involved in lipid metabolism. ACA further ameliorated age-associated changes in cardiac lipid species, particularly lysophospholipids - changes that have previously been associated with aging, cardiac dysfunction, and cardiovascular disease in humans. In the liver, ACA had pronounced effects on lipid handling in both sexes, reducing hepatic lipidosis during aging and shifting the liver lipidome in adulthood, particularly favoring reduced triglyceride (TAG) accumulation. Our results demonstrate that ACA, already in clinical use for T2DM, has broad-ranging antiaging effects in multiple tissues, and it may have the potential to increase physical function and alter lipid biology to preserve or improve health at older ages.


Assuntos
Acarbose/farmacologia , Envelhecimento/efeitos dos fármacos , Cardiomegalia/tratamento farmacológico , Coração/efeitos dos fármacos , Lipidoses/tratamento farmacológico , Hepatopatias/tratamento farmacológico , Condicionamento Físico Animal , Fatores Etários , Animais , Feminino , Inibidores de Glicosídeo Hidrolases/farmacologia , Lipidoses/metabolismo , Hepatopatias/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Fatores Sexuais
17.
Life Sci ; 263: 118490, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32979357

RESUMO

AIMS: The development of type 1 diabetes is associated with inflammatory lesion of the pancreatic islets, known as insulitis. In this study, we focused on the protective effects of acarbose against insulitis in streptozotocin (STZ)-induced diabetic mice and the underlying mechanisms. MAIN METHODS: The mouse models were established via intraperitoneal injection of multiple low-dose STZ. Blood glucose level and body weight were measured. The severity of insulitis and inflammatory parameters in pancreatic tissues were evaluated. Insulin levels in pancreas and serum were also assessed. In vitro, MIN6 ß cells were exposed to pro-inflammatory cytokines to assess the protective effects of acarbose. Cell function and apoptosis were evaluated. KEY FINDINGS: We found that acarbose administration by gavage reduced the severity of insulitis and improved insulin levels in the experimental diabetic mice. ELISA revealed decreased levels of the inflammatory response markers IL-1ß and TNF-α in mouse pancreatic tissues following acarbose treatment. In vitro, acarbose increased cell viability, decreased cell apoptosis, and improved GSIS in MIN6 ß cells exposed to pro-inflammatory cytokines. In addition, caspase-3 level and p-p53/p53 ratio in ß cells were reduced by acarbose treatment. SIGNIFICANCE: Taken together, these results revealed a novel function of acarbose in attenuating insulitis. The protective effects of acarbose elicited in vitro and in vivo were shown to be mediated, at least in part, through its anti-inflammatory action.


Assuntos
Acarbose/farmacologia , Diabetes Mellitus Experimental/fisiopatologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Células Secretoras de Insulina/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Animais , Relação Dose-Resposta a Droga , Células Secretoras de Insulina/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
18.
Molecules ; 25(8)2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32316255

RESUMO

Moderate to severe psoriasis, an immune-mediated inflammatory disease, adversely affects patients' lives. Cyclosporin A (CsA), an effective immunomodulator, is used to treat psoriasis. CsA is ineffective at low doses and toxic at high doses. Acarbose (Acar), a common antidiabetic drug with anti-inflammatory and immunomodulatory effects, reduces imiquimod (IMQ)-induced psoriasis severity. Combinations of systemic drugs are generally more efficacious and safer than higher doses of single drugs. We observed that mice treated with a combination of Acar (250 mg/kg) and low-dose CsA (10 or 20 mg/kg) exhibited significantly milder IMQ-induced psoriasis-like dermatitis and smoother back skin than those treated with Acar (250 mg/kg), low-dose CsA (10 or 20 mg/kg), or IMQ alone. The combination therapy significantly reduced serum and skin levels of Th17-related cytokines (interleukin (IL)-17A, IL-22, and IL-23) and the Th1-related cytokine tumor necrosis factor-α (TNF-α) compared with Acar, low-dose CsA, and IMQ alone. Additionally, the combination therapy significantly reduced the percentages of IL-17- and IL-22-producing CD4+ T-cells (Th17 and Th22 cells, respectively) and increased that of Treg cells. Our data suggested that Acar and low-dose CsA in combination alleviates psoriatic skin lesions by inhibiting inflammation. The findings provide new insights into the effects of immunomodulatory drugs in psoriasis treatment.


Assuntos
Acarbose/efeitos adversos , Anti-Inflamatórios/administração & dosagem , Ciclosporina/efeitos adversos , Imiquimode/efeitos adversos , Psoríase/tratamento farmacológico , Acarbose/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Ciclosporina/farmacologia , Citocinas/sangue , Citocinas/metabolismo , Modelos Animais de Doenças , Quimioterapia Combinada , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos , Psoríase/induzido quimicamente , Psoríase/imunologia , Linfócitos T Reguladores/imunologia , Fator de Necrose Tumoral alfa/metabolismo
19.
Am J Med Sci ; 359(4): 212-217, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32200914

RESUMO

BACKGROUND: Acarbose and repaglinide are two safe and effective antidiabetic agents that are especially in wide use in Asian and Middle Eastern countries. These two prandial agents share some outstanding qualities that their newer counterparts do not. While globally available in generic versions, both are oral and cheap. There is a paucity of data regarding their comparative efficacy. Herein, a head-to-head comparison of the efficacy of the two in treatment of postprandial hyperglycemia of newly-diagnosed type 2 diabetes was investigated. MATERIALS AND METHODS: One hundred and sixty-four newly-diagnosed type 2 diabetes patients with fasting plasma glucose levels of <7.2 mmol/L (130 mg/dL) but 2-hour postprandial glucose (2hPPG) levels of >10 mmol/L (180 mg/dL) were consecutively alternated between acarbose- and repaglinide-treatment for 6 months. RESULTS: Per protocol analysis, 67% of acarbose-treated patients versus 85% of repaglinide-treated patients achieved 2hPPG levels of <10 mmol/L (180 mg/dL) (P = 0.05). Treatment adherence rates were 52.4% and 72%, respectively (P < 0.02). Thirteen of the repaglinide-treated and 2 of acarbose-treated patients reported at least one episode of hypoglycemia (P < 0.03). Fasting plasma glucose, 2hPPG, glycated hemoglobin and basal insulin requirement decreased more significantly with repaglinde than acarbose (P, <0.05, <0.04, <0.04 and <0.03, respectively). Weight increased with repaglinide and decreased with acarbose (P = 0.03). There were no significant changes in LDL levels with either treatment (P = 0.58), but triglycerides decreased more significantly with acarbose treatment (P = 0.03) CONCLUSIONS: Significantly higher rates of treatment-adherence and at-target glycemic levels were seen with repaglinide treatment. Weight decreased with acarbose and increased with repaglinide treatment. Hypoglycemic episodes were much less frequent with acarbose treatment.


Assuntos
Acarbose/farmacologia , Carbamatos/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hiperglicemia/metabolismo , Hipoglicemiantes/farmacologia , Piperidinas/farmacologia , Adulto , Idoso , Glicemia/análise , Feminino , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade
20.
Biomolecules ; 10(2)2020 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-32013271

RESUMO

Adenosma bracteosum Bonati. (A. bracteosum) has been used in traditional and modern medicine in Vietnam for curing hepatitis. In this study, ethanol and aqueous extracts of A. bracteosum were evaluated for their α-glucosidase inhibitory activities and anti-hyperglycemic effects on glucose loaded hyperglycemic and streptozotocin (STZ) induced diabetic mice. The α-glucosidase inhibition of the extracts was evaluated by colorimetric assays, and the anti-diabetic activity was tested on a STZ-induced diabetic mice model. The ethanol and aqueous extracts showed a significant α-glucosidase inhibitory activity, which was more effective than acarbose at the same concentration. In the STZ-induced diabetic mice, both extracts showed a strong anti-hyperglycemic activity, with the group receiving 50 mg/kg of ethanol extract and the group receiving 50 mg/kg of aqueous extract presenting 64.42% and 57.69% reductions, respectively, in the blood glucose levels when compared with the diabetic control group, on day 21 (p > 0.05). Isoscutellarein-8-O-ß-D-glucopyranoside (IG) was identified from the ethanol extract, which showed a strong inhibitory activity against α-glucosidase, with a ten times higher potency compared with the positive control acarbose. The anti-hyperglycemic effect of IG was effectively similar to the standard drug, glibenclamide, at the same dose of 10 mg/kg (p > 0.05). These results indicated that A. bracteosum has a great antidiabetic potential.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Magnoliopsida/química , Extratos Vegetais/farmacologia , Acarbose/farmacologia , Animais , Compostos de Bifenilo/química , Glicemia/análise , Peso Corporal , Etanol/química , Feminino , Flavonoides/farmacologia , Sequestradores de Radicais Livres/farmacologia , Teste de Tolerância a Glucose , Inibidores de Glicosídeo Hidrolases/farmacologia , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Compostos Fitoquímicos/farmacologia , Picratos/química , Vietnã , alfa-Glucosidases/metabolismo , alfa-Glucosidases/farmacologia
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